Spinocerebellar ataxia

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Classification according to ICD-10
G11.1 Early onset of cerebellar ataxia
G11.2 Late-onset cerebellar ataxia
ICD-10 online (WHO version 2019)

Spinocerebellar ataxias (in English spinocerebellar ataxias , SCA for short) are a large group of clinically similar neurodegenerative diseases in humans that belong to the autosomal dominant cerebellar ataxia (ADCA) .

description

Spinocerebellar ataxias occur at a rate of one patient per 100,000 people. In affected people, the first symptoms usually appear in middle age through movement disorders , unusual eye movements , a decreased sense of direction and a decreased ability to perceive . As the disease progresses, the symptoms worsen, leading to subcortical dementia and ultimately death .

Pathologically, the disease is accompanied by a loss of Purkinje cells , the largest neurons in the cerebellum ( cerebellum ). At the genetic level, the group of spinocerebellar ataxias is very heterogeneous; 26 gene locations have already been described in the scientific literature and named SCA1 to SCA26 according to the order in which they were discovered (status 6/2005). However, the exact mutation or its exact location is not yet known for all clinical pictures.

The long-known SCA types 1, 2, 6, 7 and 17 belong to the group of trinucleotide diseases such as Huntington's disease , spinobulbar muscular atrophy type Kennedy (SBMA) and dentatorubro-pallidolucous atrophy (DRPLA), as the mutation causing the disease has an unusually long triplet repetition of the codon CAG (corresponds to the amino acid glutamine ). They have in common is furthermore an autosomal - dominant mode of inheritance and the fact is that the CAG repeat usually extended with each generation. The biological function of the proteins encoded by these genes (they are called ataxin 1, 2, 3, 6, 7 and TBP (in SCA17)) is largely unclear. Not all affected SCA genes code for proteins. The SCA8 gene, for example, codes for an antisense RNA , which from a scientific point of view initially led to great confusion, since at that time aberrant protein agglomerates were considered to be disease-causing.

Research on SCAs has been intensified in the last few years, but it is not yet so advanced that patients can expect curative therapy in the near future .

Machado Joseph Disease

Spinocerebellar ataxia 3 (SCA3) is usually referred to in the literature as Machado-Joseph disease (MJD). The cause of the disease is a mutation of the MJD1 gene on chromosome 14 gene locus q24.3-32.1, which leads to an extension of the polyglutamine region. With a share of 35% of autosomal dominant inherited cerebellar ataxias, MJD is the most common form of this disease in Germany.

SCA13

Spinocerebellar ataxia type 13 (SCA13) is a neurodegenerative disease that affects the cerebellum. SCA13 is inherited as an autosomal dominant trait.

SCA13 is caused by mutations in the potassium channel KCNC3 (Kv3.3). Three mutations have been observed to date: R420H, R423H, and F448L. R420H mutations are associated with disease in adulthood, the others with disease in childhood or congenital and slow progression.

literature

  • Buijsen RAM, Toonen LJA, Gardiner SL, van Roon-Mom WMC: Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias. In: Neurotherapeutics . tape 16 , no. 2 , April 2019, p. 263-286 , doi : 10.1007 / s13311-018-00696-y , PMID 30607747 .
  • Paulson HL, Shakkottai VG, Clark HB, Orr HAT: Polyglutamine spinocerebellar ataxias - from genes to potential treatments. In: Nat Rev Neurosci . tape 18 , no. 10 , October 2017, p. 613-626 , doi : 10.1038 / nrn.2017.92 , PMID 28855740 .
  • Schöls L, Bauer P, Schmidt T, Schulte T, Riess O: Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. In: Lancet Neurol . tape 3 , no. 5 , May 2004, pp. 291-304 , doi : 10.1016 / S1474-4422 (04) 00737-9 , PMID 15099544 .
  • Riess O, Schmidt T, Schols L: Autosomal dominant inherited spinocerebellar ataxias - clinic, genetics and pathogenesis. In: Deutsches Ärzteblatt . tape 98 , no. 23 , 2001, p. 1233-1240 .
  • Aya Kito: 1 liter of tears. (Japanese: Ichi Rittoru no Namida. German translated: '1 liter of tears').

Individual evidence

  • D. Tait: Subcellular localization of the ataxin-3 protein and aggregate analyzes in vitro and in cell culture systems. Dissertation, FU Berlin, 2000 [1] .

Web links

Individual evidence

  1. ↑ Human genetics at the University of Bochum: Ataxias, spinocerebellar autosomal dominant (SCA)